USMLE QUESTIONS:

danil hammoudi.md

sinoe medical association

volume of distribution: Vd= TOTAL AMOUNT OF DRUG IN BODY

[] OF DRUG IN THE PASMA

-WARFARIN EXERTS ITS ANTICOAGULANTS EFFECT BY:

***INHIBITING THE CARBOXYLATION OF PRO-CLOTTING FACTORS

WARFARIN BLOCKS THE VIT K-DEPENDENT STEP IN THE SYNTHESIS OF CLOTTING FACTORS BLOCKING THE STEP OF VIT K REGENERATION BY AN EPOXIDE REDUCTASE REQUIRING NADH.

-THE THERAPEUTIC EFFECT OF SODIUM WARFARIN IS DEPENDENT ON THE HALF LIVES OF ALL THE FOLLOWING COAGULATION FACTORS:

***II

***VII

***IX

***X

· SODIUM WARFARIN IS THE PROTOTYPE OF THE COUMARIN DERIVED ANTICOAGULANTS.

· 8-12 HOURS ARE REQUIRED FOR ACTION .

· IT IS 99% BOUND TO PLASMA ALBUMIN

· METABOLIZED IN THE LIVER-EXCRETED IN THE URINE AND FECES.

· FACTORS AFFECTING ACTIVITY:

***CONDITIONS THAT INCREASE THE RESPONSE TO ANTICOAGULANTS INCLUDE :

+++VIT K DEFICIENCY

+++HYPERMETABOLIC STATES,SUCH HYPERTHYROIDISM.

+++DEBILATING STATES, SUCH CONGESTIVE HEART FAILURE

+++AGE: THE OLDER THE PATIENT, THE GREATER THE RESPONSE TO THESE COAGULANTS.

***WARFARIN INDUCE MICROSOMIAL ENZYMES

***EXCESSIVELY REDUCED LEVELS OF PROTHROMBIN WILL RESULT IN HEMORRHAGE.

***DURING PREGNANCY, VIT K DEPENDANT FACTORS ARE INCREASED, RESULTING IN DECREASED RESPONSIVENESS TO ORAL ANTICOAGULANTS.

· SINCE HEPARIN DOES NOT CROSS THE PLACENTA, IT IS CONSIDERED SAFE FOR THE FETUS.

THERAPEUTIC USES:

***SECONDARY PROPHYLACTIC TRT OF

· VENOUS THROMBOSIS

· PULMONARY EMBOLISM.

· PREVENT THE RECURRENCE OR EXTENSION OF VENOUS THROMBUS FORMATION .

-SINCE ORAL ANTOCOAGULANTS HAVE NO EFFECT ON PLATELETS, THEY ARE NOT USED IN THE TRT OF TROMBOTIC DISEASE IN THE ARTERIAL SYSTEM.

ADVERSE EFFECTS:

-WARFARIN NECROSIS =PAINFULL ERYTHEMATOUS PATCH ON THE SKIN ,WHICH CAN PROGRESS TO GANGRENE. 3-10DAYS OCCURS OF STARTING WARFARIN THERAPY.

THROMBI OCCUR IN THE VASCULATURE OF AFFECTED TISSUE.

- A PURPLE TOE SYNDROME CAN OCCUR 3-8 WEEKS AFTER STARTING WARFARIN THERAPY . IT IS CAUSED BY CHOLESTEROL EMBOLI FROM ATHEROMATOUS PLAQUES, FOLLOWING BLEEDING INTO THE PLAQUES.

- WARFARIN IS CONTRE INDICATED IN PREGNANCY BUT NOT FOR THE NURSING MOTHER SINCE IT IS NOT EXCRETED IN MILK.

REVERSAL ANTICOAGULANT EFFECTS:

· VIT K1 [PHYTONADIONE] WILL ENHANCE TO RECOVERY

· FOR SEVERE HEMORRHAGE , PHYTONADIONE IS GIVEN INTRAVENOUSLY . PT RETURN TO NORMAL 6-12 HOURS.

·

· DRUGS INTERACTIONS WITH ORAL ANTICOAGULANTS

DRUGS EFFECT ON RESPONSE TO ANTI COAG MECHANISM

acetylsalicylic acid i decreased ADP release by platelets , IMPAIRING PLATELET AGGREGATION

BARBITURATES- D INDUCE DRUG MICROSOMAL METABOLIZING SYSTEM

GLUTHEMIDE

CHOLESTYRAMINE D DECREASE HYPOPROTHROMBINEMIA; INCREASE PLASMA CLEARANCE OF DRUG.

CIMETIDINE I UNKNOWN

CLOFIBRATE I DECREASE PLATELET ADHESIVENESS

INCREASE TURNOVER OF VITAMIN K-DEPENDENT FACTORS

DISULFIRAM-METRONIDAZOLE I

HEPARIN:

· ANTITHROMBIN FACTOR

· IT IS AN ANTIPLATELET DRUG

· IT HAS NO EFFECT ON THE SYNTHESIS OF BLOOD COAGULATION FACTORS

· DOES NOT BLOCK PROTHROMBIN SYNTHESIS IN THE LIVER AS DO THE ORAL ANTICOAGULANTS

· IHIBITS CONVERSION OF PT

· INTERFERE WITH FORMATION OF FIBRIN.